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Originally published in Science Express on 6 November 2003
Science 19 December 2003:
Vol. 302. no. 5653, pp. 2124 - 2126
DOI: 10.1126/science.1088697
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Reports

Yeast Life-Span Extension by Calorie Restriction Is Independent of NAD Fluctuation

Rozalyn M. Anderson,1* Magda Latorre-Esteves,1* Ana Rute Neves,2 Siva Lavu,1,3 Oliver Medvedik,1 Christopher Taylor,3 Konrad T. Howitz,3 Helena Santos,2 David A. Sinclair1{dagger}

Calorie restriction (CR) slows aging in numerous species. In the yeast Saccharomyces cerevisiae, this effect requires Sir2, a conserved NAD+-dependent deacetylase. We report that CR reduces nuclear NAD+ levels in vivo. Moreover, the activity of Sir2 and its human homologue SIRT1 are not affected by physiological alterations in the NAD+:NADH ratio. These data implicate alternate mechanisms of Sir2 regulation by CR.

1 Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston MA 02115, USA.
2 Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Rua da Quinta Grande 6, Apartado 127, 2780-156 OEIRAS, Portugal.
3 Biomol Research Laboratories, Inc., 5120 Butler Pike, Plymouth Meeting, PA 19462, USA.



* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: David_Sinclair{at}hms.harvard.edu

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